The following discussion is provided solely to assist the understanding of the reader, and does not constitute an admission that any of the information discussed or references cited constitute prior art to the present invention.
Control of blood glucose concentrations in diabetic patients has been shown to decrease the frequency and severity of long-term microvascular and neurologic complications of the disease. It has been found that the rate of formation of glycated hemoglobin is directly related to the glucose concentration in blood. As a result, in the management of glucose levels, measurement of glycated hemoglobin is used to determine how well blood glucose concentration has been managed over extended time periods.
Typically, the average lifetime for red blood cells is about 90-120 days. Therefore, determination of the percent glycation of hemoglobin correlates with the average glucose concentration during that period of time, and especially over the previous 2-3 months. Therefore, the percent glycated hemoglobin is an indicator of glycemic control over that time period.
Hemoglobin variants, such as HbS, HbC, HbD, HbE, may have a shorter average lifetime and different glycation rates and can have an effect on the correlation of % HbA1C to average glucose concentration, hence effecting the clinical value of the HbA1C result.
Knowing if a common variant is present is an important factor when assessing glycemic control, especially in a screening environment.
It has also been found that glucose attaches to non-hemoglobin proteins in blood, for example the abundant protein, albumin. Since the circulating half-life for albumin is about 20 days, the concentration (or ratio) of glycated albumin is a measure of the average glucose concentration over the previous 2-3 weeks.
Some methods to determine the concentration or percent of glycated proteins have utilized dihydroxyboryl compounds which bind to the 1,2 cis diols of the carbohydrate of glycated proteins to separate them from non-glycated proteins. Such methods include those described in U.S. Pat. Nos. 4,269,605, 5,284,777, 5,110,745, 4,861,728 PCT Appl. WO 96/03657), and PCT application WO 9840750, which are incorporated herein by reference in their entireties.